Biomedical subjects

G S Hamilton

Publications and source records attributed to G S Hamilton.

24 records · Page 2Linked to original sources

PubMed1993

Gadolinium-DTPA enhanced MRI demonstrates uterine vascular changes associated with artificially induced decidualization and ovoimplantation in rats.

Gadolinium-DTPA enhanced magnetic resonance (MR) imaging has been used to demonstrate uterine vascular changes during ovoimplantation and artificially induced decidualization in rats. Evans blue dye and Gd-DTPA were injected i.v. into rats 10 h after unilateral decidualization was induced by injection of sesame oil into the lumen of one uterine horn. Animals were killed various times later and uteri were removed, T1-weighted proton imaging was performed, and mean image intensities for stimulated and control uterine horns were calculated by computer-assisted image analysis. Macroscopic bluing confined to stimulated horns was apparent 5 min after tracer injection and increased in intensity until the experiment was terminated at 320 min. Analysis of MR images showed that mean image intensity of control horns did not change significantly at any time after injection of the Gd-DTPA and Evans blue whereas mean image intensity of stimulated horns increased significantly by 5 min after injection, peaked at 20 min, and returned to values not different from controls by 320 min. T1-weighted images of day 6 pregnant rats injected with Gd-DTPA and Evans blue revealed patterns of image enhancement that matched those of macroscopic bluing. Uterine concentrations of radioactivity after injection of 153Gd-DTPA indicated that increased extracellular fluid volume (ECFV) produces the image enhancement of stimulated horns since the tracer permeates the extracellular fluid of both horns. Gd-DTPA-enhanced MR imaging of uteri after deciduogenic stimulation revealed significant image enhancement for stimulated horns at both 9 and 27 h after stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Uterine extracellular fluid volume and blood flow after artificial uterine stimulation to rats differentially sensitized for the decidual cell reaction.

Uterine extracellular fluid volume (ECFV) and blood flow (BF) were assessed after unilateral intrauterine injection of sesame oil to rats given either ideal sensitization for the decidual cell reaction or one of several forms of non-ideal sensitization. The study was intended to determine how changes in uterine ECFV and BF might contribute to the Evans blue dye reaction that can be elicited during early decidualization. Uterine ECFV was determined by the uterine volume of distribution of 51Cr-EDTA after its i.v. injection; BF was determined by the radioactive microsphere technique. ECFV was significantly greater in oil-injected than in control horns by 8 h after deciduogenic stimulation, reaching a maximum of 0.63 +/- 0.06 microliter/mg (p < 0.05) in oil-injected horns at 16 h. Ideal temporal sensitization and sensitization with estrogen both were essential to obtain the significantly increased ECFV in stimulated horns. Although absolute uterine BF increased to oil-injected horns, the increase matched uterine weight gains, making relative uterine BF similar for both horns (3-4 microliters/min/mg) at all times after unilateral deciduogenic stimulation. Ideal sensitization did not significantly alter the relative uterine BF. The increase in ECFV occurs at a similar time and requires the same ideal sensitization as the stimulation-induced increase in endometrial vascular permeability described previously, suggesting that these events are under similar control. We suggest that enzymatic changes to the uterine extracellular matrix may contribute to the Evans blue reaction by creating a larger compartment into which protein-dye complexes may diffuse.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Behavioral pharmacology of NPC 17742, a competitive N-methyl-D-aspartate (NMDA) antagonist.

The behavioral effects of the competitive N-methyl-D-aspartate (NMDA) antagonist 2R,4R,5S-2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoate (NPC 17742) were compared with those of its parent compound, 2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoate (NPC 12626), and other reference agents in a variety of operant-based tasks in rodents. In mice trained to lever press under a fixed-ratio (FR) 20 reinforcement schedule, NPC 17742 was 6.2 times more potent than NPC 12626 and equipotent with the competitive NMDA antagonist [E]-2-amino-4-methyl-5-phosphono-3-penteneoic acid (CGP 37849) in reducing rates of responding. NPC 17742 was also 3.5 and 4.5 times more potent than [+-]cis-4-phosphonomethyl-2-piperidine carboxylate (CGS 19755) and [+-] 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonate (CPP), respectively, and half as potent as 3SR, 4aRS, 6SR, 8aRS-6-(phosphonomethyl)-1,2,3,4,4a,5,6,7,8,8a- decahydroisoquinoline-3-carboxylate (LY 274614) in this paradigm. In rats trained to discriminate 4.0 mg/kg NPC 17742 from saline, NPC 17742 was 5.7 times more potent than NPC 12626 in substituting for NPC 17742. CGS 19755 also substituted for NPC 17742, but a maximum of only 50% NPC 17742 lever responding was observed after LY 274614 administration. In rats trained to lever press in a modified Geller-Seifter procedure, NPC 17742 and NPC 12626, like the benzodiazepine chlordiazepoxide, increased rates of punished responding. Neither tolerance nor sensitization to the anti-punishment effects were observed upon administration of NPC 17742 for 5 consecutive days. The results are consistent with NPC 17742 being a potent, systemically active compound whose behavioral effects are mediated through interaction with the NMDA receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗

PubMed1993

Pharmacological profile of NPC 17742 [2R,4R,5S-(2-amino-4,5-(1, 2-cyclohexyl)-7-phosphonoheptanoic acid)], a potent, selective and competitive N-methyl-D-aspartate receptor antagonist.

2R,4R,5S-(2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid) (NPC 17742), the most potent isomer of the mixture 2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid (NPC 12626), was evaluated for activity in tests associated with receptors for excitatory amino acids. In receptor binding assays, NPC 17742 was selective for the N-methyl-D-aspartate (NMDA) receptor with a potency comparable to that of D(-, -3-(2-carboxypiperazine-4-yl)propyl-1-phosphonic acid. Like (+/-)cis-4-phosphono-methyl-2-piperidine carboxylic acid (CGS 19755) and (+/-)(E)-2-amino-4-methyl-5-phosphono-3-penteneoic acid (CGP 37849), NPC 17742 competitively inhibited NMDA-induced enhancement of 1-[(2-thienyl)cyclohexyl]piperidine binding to the NMDA receptor ionophore and partially inhibited [3H]glycine binding to strychnine-insensitive sites. In contrast, NPC 17742 and CGP 37849 inhibited Mg(++)-stimulated 1-[(2-thienyl)cyclohexyl]piperidine binding in a noncompetitive fashion. In voltage-clamped Xenopus oocytes expressing excitatory amino acid receptors, NPC 17742 (pKB = 6.91) was equipotent with CGP 37849 (pKB = 7.17) in inhibiting NMDA-induced inward currents. Likewise, NPC 17742 (ED50 = 2.68 mg/kg) was equipotent with CGP 37849 and CGS 19755 in blocking NMDA-induced convulsions, but was less potent than these two compounds in the maximal electroshock test. Unlike CGP 37849 or CGS 19755, NPC 17742 potently antagonized seizures induced by pentylenetetrazol. In a model of global ischemia, low doses of NPC 17742 given either before or after ischemic result were effective in blocking damage to hippocampal CA1 neurons. The pharmacologic responses to NPC 17742 occurred at doses 30- to 300-fold lower than the acute lethal dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

PubMed1991

The superovulation of synchronous adult rats using follicle-stimulating hormone delivered by continuous infusion.

The estrous cycles of adult female rats were synchronized with an LHRH agonist on the morning of Day -4 (Day 0 = day of mating). On Day -2, animals received s.c. implants of continuous-infusion osmotic minipumps containing different doses of an FSH preparation (Folltropin) in combination with hCG at various ratios of hCG:FSH or were given single injections of eCG in doses ranging from 15 IU to 60 IU. Rats infused with the optimal dose (3.4 U/day) of FSH ovulated 44.1 +/- 5.4 oocytes/rat while rats treated with the most effective dose (60 IU) of eCG ovulated only 20.5 +/- 4.3 oocytes/rat on the morning of Day 1. The inclusion of hCG in pumps at ratios from 0.188:1 to 0.75:1 (hCG:FSH) had no significant effect on ovulation rate. The importance of synchronization of estrus in successful superovulation was demonstrated by the finding that only 70% of the unsynchronized animals ovulated (29.1 +/- 4.8 oocytes/rat) whereas 95% of the synchronized animals ovulated (51.0 +/- 3.6 oocytes/rat). Oocyte viabilities were assessed by determining fertilization rates and embryonic development in vivo following mating with fertile males. In rats superovulated by use of the FSH regimen, 92% (39.0 +/- 4.1) of the recovered embryos were 1-cell zygotes on Day 1, 89% (36.3 +/- 5.6) were at the 2-cell embryo stage of development on Day 2, and 88% (28.8 +/- 2.2) were at the morula and blastocyst stages on Day 5 following mating on Day 0. The high ovulation rates and oocyte viability in rats receiving infusions of Folltropin following estrus synchronization offer a reliable method for superovulation of adult rats.

Animals↗

PubMedDate not supplied

Early identification of sites of embryo implantation in rats by means of gadolinium-enhanced MR imaging.

To determine if magnetic resonance (MR) imaging techniques can be used to examine sites of embryo implantation in intact rats, pregnant animals were imaged with gadopentetate dimeglumine-enhanced MR imaging approximately 10 hours after initiation of implantation on day 5 of pregnancy. T1-weighted, three-dimensional SPGR (spoiled gradient-recalled acquisition in the steady state) sequences were used to image the volume of abdomen containing the uterine horns before and after injection of gadopentetate dimeglumine into a femoral venous catheter. While unenhanced images provided little detail in uterine tissue, analysis of the gadolinium-enhanced abdominal images with interactive vascular imaging allowed easy identification of sites of embryo implantation along both uterine horns in four of four pregnant rats. These punctate patterns of enhancement match those of macroscopic bluing after injection of Evans blue dye. Similar gadolinium-enhanced MR imaging of nonpregnant rats produced only a slight, generalized enhancement of entire uterine horns. The authors conclude that local increases in extracellular fluid volume, vascular permeability, and blood flow in the uterus may all contribute to the gadolinium enhancement of the implantation sites. They propose that this approach can be used in experimental settings to provide information regarding embryo implantation unaccessible with traditional approaches. In clinical settings, gadolinium-enhanced MR imaging may be used to examine potential causes of infertility, including luteal phase defects.

Animals↗